The incidence of melanoma and non‐melanoma skin cancer is continuing to increase worldwide. Melanoma is the sixth most common cancer in the United States, making skin cancer a significant public health issue. Photo chemoprevention with natural products is an effective strategy for the control of cutaneous neoplastic. Polyphenols from fruits have been shown to protect the skin from the adverse effects of solar UVR, cancer, and the growth of cancer stem cells. In particular, blueberries are known for their high concentration of phenolic compounds that have the high antioxidant capacity, and their effectiveness in reducing UV damage and, therefore, skin cancer. In Matar's lab, we have shown that Polyphenol-Enriched Blueberry Preparation (PEBP), derived from biotransformation of blueberry juice through fermentation, is effective for targeting skin cancer stem cell proliferation in different skin cancer cell lines. We predicted that PEBP affects melanoma skin cancer stem cells (MCSCs) epigenetically by targeting miRNA pathways. We observed the effects of PEBP on sphere growth and cell motility in vitro. We performed RT2-qPCR analyses to determine PEBP influence on miRNA in B16F10 spheres. We transfected B16F10 cells with miR-200b and performed western blotting analyses. Our results demonstrated that PEBP reduced sphere growth and cell migration, and up regulated miR-200b expression in different biological settings. Inhibition of miR-200b increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression. Consequently, PEBP may influence MCSCs through miRNA pathways. Elucidating the mechanisms by which PEBP modulates CSCs biological behavior by controlling miRNAs will enhance our understanding of the molecular mechanisms in skin cancer chemoprevention and might result in their use as natural photo-protectants in skin cancer.

INTRODUCTION: Pulmonary hypoplasia causes high morbidity and mortality in congenital diaphragmatic hernia (CDH) patients. MiR-10a and miR-200b are overexpressed in human CDH lungs. We aimed to define their roles in lung development. METHODS: We profiled miR-10a expression with RT-qPCR and in situ hybridization using a nitrofen rat model for CDH. The effects of miR-10a on airway branching were evaluated in lung explants. MiR-200b’s role in airway branching was assessed in miR-200b knockout lung explants. Crossing miR-200b knockout mice with CFP-E-Cadherin was used to evaluate miR-200b’s effects on epithelial differentiation. RESULTS: Expression of miR-10a was altered in the nitrofen model and miR-10a mimics reversed lung hypoplasia in vitro. Heterozygous miR-200b lung explants displayed reduced airway branching. CFP-E-Cadherin/miR-200b knockout lung explants showed reduced epithelial expression. CONCLUSION: Both miR-10a and miR-200b are critical for lung development and CDH. Normalizing their expression may reverse lung hypoplasia and reduce the associated morbidity and mortality in CDH. / February 2016